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Cell Rep. 2018 May 15;23(7):2056-2069. doi: 10.1016/j.celrep.2018.04.074.

An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

Author information

1
Molecular Neuropharmacology and Genetics Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute - Mærsk Tower, University of Copenhagen, 2200 Copenhagen N, Denmark.
2
Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York City, NY 10065, USA.
3
Bionanotechnology and Nanomedicine Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Chemistry, and Nano-Science Center, University of Copenhagen, 2300 Copenhagen Ø, Denmark.
4
Molecular Neuropharmacology and Genetics Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute - Mærsk Tower, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: gether@sund.ku.dk.
5
Molecular Neuropharmacology and Genetics Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute - Mærsk Tower, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: kennethma@sund.ku.dk.

Abstract

BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis.

KEYWORDS:

BAR domains; Drosophila; ICA69; INS-1E cells; PICK1; arfaptin; dense core vesicle biogenesis; insulin secretory granules; membrane curvature sensing; weight regulation

PMID:
29768204
DOI:
10.1016/j.celrep.2018.04.074
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